Kaposi's sarcoma is not an uncommon complication of HIV disease. The treatment of Kaposi's sarcoma is complicated by bone marrow toxicity, opportunistic infections, progressive HIV disease, including progressive immunodeficiency, increasing viral burden increasing virulence of HIV and eventual failure of current anti-retroviral therapies. Treatments which enhance suppression of HIV, immune function and focuses on the pathogenesis of Kaposi's sarcoma are needed. Several single agent and combination chemotherapy regimens result in tumor regression. Interferon (IFN) alpha-2a has been associated with tumor responses, and in combination with zidovudine (ZDV) may result in greater anti-tumor responses at lower doses of IFN alpha-2a. The HIV-1 tat gen and the TAT protein has been implicated in the pathogenesis of Kaposi's sarcoma. A tat gene antagonist, Ro 24-7429, inhibits HIV in acutely and chronically infected cells and is active against zidovudine-resistant strains. Thus, Ro 24-7429 represents a novel approach for the treatment of patients with HIV disease and Kaposi's sarcoma. Two phase I/II studies to evaluate the role of combination therapies for patients with HIV-related Kaposi's sarcoma are proposed. The first study is designed to extend the observation that IFN alpha-2a and ZDV is useful in the treatment of patients with HIV-related Kaposi's sarcoma by including a third drug, the tat gene antagonist (Ro 24-7429), that inhibits HIV post transcription and may inhibit specific cytokine function implicated in the pathogenesis of Kaposi's sarcoma. The first phase I/II study proposed will evaluate the safety, pharmacokinetic parameters and preliminary efficacy of combination therapy with Ro 24-7429, IFN alpha-2a and ADV in patients with earlier stages of HIV-related Kaposi's sarcoma. Two doses of Ro 24- 7429 will be tested (50 mg TID and 100 mg TID) and two doses of IFN alpha-2a (4.5 MIU QD and 9.0 MIU QD). Pharmacokinetic studies will be done week 1 and 12 to determine the pharmacokinetic disposition of Ro 24- 7429 when given with IFN alpha-2a and ZDV. Tumor responses will be monitored. To further evaluate the anti-HIV activity of this combination, changes in CD4+ cells, serum p24 antigen levels and copy numbers of plasma HIV RNA by PCR will be evaluated. HIV+ supernatants and PBMCs will be stored for future studies which could include evaluation of mRNA in cells and resistance studies. The second study will evaluate single agent chemotherapy, vinblastine, in the treatment of patients with non-visceral Kaposi's sarcoma when given with Ro 24-7429 and monitor safety and tumor responses.